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Trial registered on ANZCTR


Registration number
ACTRN12621001409864
Ethics application status
Approved
Date submitted
1/10/2021
Date registered
20/10/2021
Date last updated
23/03/2022
Date data sharing statement initially provided
20/10/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Comparative assessment of the absorption of a generic formulation of 5 mg bis [(E)-7-[4-(4-fluorophenyl)- 6-isopropyl-2- [methyl(methylsulfonyl) amino]pyrimidin-5-yl] (3R,5S)-3,5-dihydroxyhept-6-enoic acid] calcium salt orally disintegrated tablet (ODT) against the innovator 40 mg bis [(E)-7-[4-(4-fluorophenyl)- 6-isopropyl-2- [methyl(methylsulfonyl) amino]pyrimidin-5-yl] (3R,5S)-3,5-dihydroxyhept-6-enoic acid] calcium salt oral tablet conducted under fasting conditions in healthy volunteers.
Scientific title
A single dose, randomized, open label, pharmacokinetic study to compare the bioavailability of 5 mg bis [(E)-7-[4-(4-fluorophenyl)- 6-isopropyl-2- [methyl(methylsulfonyl) amino]pyrimidin-5-yl] (3R,5S)-3,5-dihydroxyhept-6-enoic acid] calcium salt orally disintegrated tablet (ODT) taken sublingually against the innovator 40 mg bis [(E)-7-[4-(4-fluorophenyl)- 6-isopropyl-2- [methyl(methylsulfonyl) amino]pyrimidin-5-yl] (3R,5S)-3,5-dihydroxyhept-6-enoic acid] calcium salt oral tablet conducted under fasting conditions in healthy volunteers.
Secondary ID [1] 305447 0
None
Universal Trial Number (UTN)
U1111-1268-1559
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
bis [(E)-7-[4-(4-fluorophenyl)- 6-isopropyl-2- [methyl(methylsulfonyl) amino]pyrimidin-5-yl] (3R,5S)-3,5-dihydroxyhept-6-enoic acid] calcium salt is indicated in patients with no hyperchloesterolaemia as an adjunct to diet when the response to diet and exercise is inadequate. 323824 0
Condition category
Condition code
Cardiovascular 321331 321331 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Single dose, crossover study design whereby each participant receives the test formulation of
1 x 5 mg bis [(E)-7-[4-(4-fluorophenyl)- 6-isopropyl-2- [methyl(methylsulfonyl) amino]pyrimidin-5-yl] (3R,5S)-3,5-dihydroxyhept-6-enoic acid] calcium salt orally disintegrated tablet (ODT) on one occasion and the innovator formulation of 1 x 40 mg bis [(E)-7-[4-(4-fluorophenyl)- 6-isopropyl-2- [methyl(methylsulfonyl) amino]pyrimidin-5-yl] (3R,5S)-3,5-dihydroxyhept-6-enoic acid] calcium salt oral tablet on one occasion with each dose separated by a two week washout period. The intervention for this trial is the test ODT formulation.

No water is allowed for 1 hour prior to dosing until 1 hour after dosing (except for the water consumed with the comparator treatment).

Participants are required not to eat for 10 hours before dosing and to fast for approximately 4 hours after each dose.

Bathroom visits will be supervised to ensure no unauthorized water or food intake and for personal safety.

Participants will be confined at the Clinical Site for 12 hours prior to dosing to ensure compliance and for 24 hours after dosing.

Participants will be monitored for adverse events throughout the study.

Standard meals will be consumed at the Clinical Site with no additional food intake allowed.
The actual meals provided will be determined based on the menu in operation at the time of study conduct. As a guide the lunch and dinner meals will consist of a medium sized serving of meat, vegetables and dessert with fruit available in the evening. A vegetarian option may be available. The meals will not contain any chocolate or citrus products.

Alcohol breath testing and dipstick drugs of abuse tests will be performed upon each participant reporting to the clinical site 12 hours prior to dosing.

Screening procedures including laboratory tests and medical examinations will be completed to assess the health of the participants. Study exit procedures will be completed within one week after receiving the last dose.

The test product will be administered under the tongue (sublingually) until completely dissolved and the reference dose will be taken orally with 240 ml of water at ambient temperature. The Reference medication must be swallowed whole and a mouth check will be conducted to ensure that each medication has been taken as directed.
Intervention code [1] 321839 0
Treatment: Drugs
Comparator / control treatment
Single dose, crossover study whereby each participant receives the test formulation 1 x 5 mg bis [(E)-7-[4-(4-fluorophenyl)- 6-isopropyl-2- [methyl(methylsulfonyl) amino]pyrimidin-5-yl] (3R,5S)-3,5-dihydroxyhept-6-enoic acid] calcium salt orally disintegrated tablet (ODT) on one occasion and the innovator formulation of 1 x 40 mg bis [(E)-7-[4-(4-fluorophenyl)- 6-isopropyl-2- [methyl(methylsulfonyl) amino]pyrimidin-5-yl] (3R,5S)-3,5-dihydroxyhept-6-enoic acid] calcium salt oral tablet on one occasion with each dose separated by a two week washout period. The comparator/control for this trial is the innovator formulation.
Control group
Active

Outcomes
Primary outcome [1] 329115 0
To evaluate the pharmacokinetics (as summarised by Cmax and AUC) of the test formulation relative to that of the reference formulation. All plasma samples will be assayed for bis [(E)-7-[4-(4-fluorophenyl)- 6-isopropyl-2- [methyl(methylsulfonyl) amino]pyrimidin-5-yl] (3R,5S)-3,5-dihydroxyhept-6-enoic acid] calcium salt using one fully validated LC/MS/MS method. Validation will be conducted to comply with FDA guidelines.
Timepoint [1] 329115 0
Orally disintegrating tablet:
The sampling intervals will be at 0, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 20, 24, 32, 48, 56 and 72 hours post dosing.

Oral tablet:
The sampling intervals will be at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 10, 12, 16, 20, 24, 32, 48, 56 and 72 hours post dosing.
Secondary outcome [1] 401518 0
Time to maximum peak concentration (Tmax) will be determined by plasma sample analysis. Tmax will be the time where the maximum concentration occurred in the sample points.
Timepoint [1] 401518 0
Orally disintegrating tablet:
The sampling intervals will be at 0, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 20, 24, 32, 48, 56 and 72 hours post dosing.

Oral tablet:
The sampling intervals will be at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 10, 12, 16, 20, 24, 32, 48, 56 and 72 hours post dosing.

Eligibility
Key inclusion criteria
Healthy participants
Aged between 18 and 55 years
Non-smoker
BMI greater than or equal to 18.5 and less than 29.9 inclusive
Normal, healthy individuals as determined by medical history, physical examination, ECG, blood pressure and laboratory tests
Drug free as determined by urine drug testing
Able to comply with the study restrictions
Able to provide written informed consent
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Asian heritage.
Clinically significant medical conditions
History of conditions that might interfere with the absorption, distribution, metabolism or excretion of the drug
History of alcohol or drug abuse or dependency
Participation in a drug study within 60 days of the start of the study
Sensitivitie to the study drug or excipients
Individuals for whom the Clinical Investigator believes, for any reason, that participation would not be an acceptable risk

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Each participant will be identified by a 3 digit screening number and a 2 digit subject number. The screening number will be issued once the participant has given written consent to participate in the study and the two digit study number (randomisation number) after acceptance into the study. Randomization will be performed using a randomisation table created by computer software (i.e. computerized sequence generation).
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Bio-availability
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
15/11/2021
Actual
29/11/2021
Date of last participant enrolment
Anticipated
Actual
29/11/2021
Date of last data collection
Anticipated
Actual
17/12/2021
Sample size
Target
16
Accrual to date
Final
16
Recruitment outside Australia
Country [1] 24155 0
New Zealand
State/province [1] 24155 0
Otago

Funding & Sponsors
Funding source category [1] 309805 0
Commercial sector/Industry
Name [1] 309805 0
Aspen Pharmacare Australia
Country [1] 309805 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Zenith Technology Corporation Limited
Address
PO Box 1777
Dunedin 9054
Country
New Zealand
Secondary sponsor category [1] 310835 0
None
Name [1] 310835 0
Address [1] 310835 0
Country [1] 310835 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309552 0
Northern A Health and Disability Ethics Committee
Ethics committee address [1] 309552 0
Ethics committee country [1] 309552 0
New Zealand
Date submitted for ethics approval [1] 309552 0
21/07/2021
Approval date [1] 309552 0
03/09/2021
Ethics approval number [1] 309552 0
21/NTA/130

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 114562 0
Dr Noelyn Hung
Address 114562 0
Zenith Technology Corp Ltd
PO Box 1777,
Dunedin 9054
Country 114562 0
New Zealand
Phone 114562 0
+64 21 482 148
Fax 114562 0
+64 3 477 9605
Email 114562 0
noelyn.hung@otago.ac.nz
Contact person for public queries
Name 114563 0
Linda Folland
Address 114563 0
Zenith Technology Corp Ltd
PO Box 1777,
Dunedin 9054
Country 114563 0
New Zealand
Phone 114563 0
+64 3 477 9669
Fax 114563 0
+64 3 477 9605
Email 114563 0
linda.folland@zenithtechnology.co.nz
Contact person for scientific queries
Name 114564 0
Tak Hung
Address 114564 0
Zenith Technology Corp Ltd
PO Box 1777,
Dunedin 9054
Country 114564 0
New Zealand
Phone 114564 0
+64 3 477 9669
Fax 114564 0
+64 3 477 9605
Email 114564 0
tak.hung@zenithtechnology.co.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
All data will be compiled into a final report that is the property of the sponsor company. All participant data will be provided in summary format and result of the study only will be reported


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.